An overview of human psychophysical studies of taste and smell indicates that there are significant chemosensory losses with age, and these losses can affect nutritional status and quality of life. Olfactory losses can also reduce the ability to detect fire, dangerous fumes, and polluted environments. Little is known about the role that medications play in these age-related losses of taste and smell. In 1988, Americans spent $27.1 billion on prescription medications. In that year, the elderly constituted 12 percent of the total population but accounted for 35 percent of the prescription drug expenditures. Epidemiological studies indicate that the mean number of medications used by community-dwelling elderly over 65 ranges from 2.9 to 3.7 medications, and this number increases significantly to as high as 7.2 or more for elderly in nursing homes. Most reports of taste and smell losses from medications are based on clinical reports rather than experimental data. The purpose of this proposal is to use quantitative experimental methods to measure the effect of medications used by the elderly on the senses of taste and smell. The effect of drugs on taste perception at the periphery will be assessed in young and elderly subjects by psychophysical techniques after direct topical application of the pharmaceutical compounds to the tongue. Experimental subjects in topical studies will be taking no medications. These studies will be performed because drugs are secreted into the saliva at concentrations that can modify taste transduction. Pharmaceutical compounds will be applied topically at concentrations from 0.1 M to 1 mM to determine the salivary concentration of a drug that produces a taste change. Exposure to a drug will never exceed 1/1000 of a dose. In addition, elderly patients will be tested for taste and smell acuity prior to administration of these drugs by their physicians as well as during the course of treatment. This will permit the development of a data base that will provide accurate data on frequency of taste and smell changes that result from medications. The effect of medications on taste and smell perception in the elderly will be evaluated according to: 1) the therapeutic class of the drug (e.g., antihypertensive, diuretic, anticholinesteremic), 2) the type of peripheral receptor or ion channel to which the drug binds (e.g., cholinergic or dopamine receptor; calcium channel); and/or 3) the physicochemical characteristics of the drug (e.g., lipid:water partition coefficients). The ultimate goal is to find methods to alleviate taste and smell losses that result from use of medications.